Genetic mechanism of body size variation in groupers:Insights from phylotranscriptomics

Animal body size variation is of particular interest in evolutionary biology,but the genetic basis remains largely unknown.Previous studies have shown the presence of two parallel evolutionary genetic clusters within the fish genus Epinephelus with evident divergence in body size,providing an excellent opportunity to investigate the genetic basis of body size variation in vertebrates.Herein,we performed phylotranscriptomic analysis and reconstructed the phylogeny of 13 epinephelids originating from the South China Sea.Two genetic clades with an estimated divergence time of approximately 15.4 million years ago were correlated with large and small body size,respectively.A total of 180 rapidly evolving genes and two positively selected genes were identified between the two groups.Functional enrichment analyses of these candidate genes revealed distinct enrichment categories between the two groups.These pathways and genes may play important roles in body size variation in groupers through complex regulatory networks.Based on our results,we speculate that the ancestors of the two divergent groups of groupers may have adapted to different environments through habitat selection,leading to genetic variations in metabolic patterns,organ development,and lifespan,resulting in body size divergence between the two locally adapted populations.These findings provide important insights into the genetic mechanisms underlying body size variation in groupers and species differentiation.

Positively selected genes of the Chinese tree shrew （Tupaia belangeri chinensis） locomotion system

While the recent release of the Chinese tree shrew （Tupaia belangeri chinensis） genome has made the tree shrew an increasingly viable experimental animal model for biomedical research, further study of the genome may facilitate new insights into the applicability of this model. For example, though the tree shrew has a rapid rate of speed and strong jumping ability, there are limited studies on its locomotion ability. In this study we used the available Chinese tree shrew genome information and compared the evolutionary pattern of 407 locomotion system related orthologs among five mammals （human, rhesus monkey, mouse, rat and dog） and the Chinese tree shrew. Our analyses identified 29 genes with significantly high co （Ka/Ks ratio） values and 48 amino acid sites in 14 genes showed significant evidence of positive selection in the Chinese tree shrew. Some of these positively selected genes, e.g. HOXA6 （homeobox A6） and AVP （arginine vasopressin）, play important roles in muscle contraction or skeletal morphogenesis. These results provide important clues in understanding the genetic bases of locomotor adaptation in the Chinese tree shrew.

Comparative transcriptomes reveal the disjunction adaptive strategy of Thuja species in East Asia and North America

The genus Thuja is ideal for investigating the genetic basis of the East Asia-North America disjunction.The biogeographical background of the genus is debatable and an adaptive strategy is lacking.Through the analysis and mining of comparative transcriptomes,species differentiation and positively selected genes(PSGs)were identified to provide information for understanding the environmental adaptation strategies of the genus Thuja.De novo assembly yielded 44,397-74,252 unigenes of the five Thuja species with contig N50length ranging from 1,559 to 1,724 bp.Annotations revealed a similar distribution of functional categories among them.Based on the phylogenetic trees constructed using the transcriptome data,T.sutchuenensis was divided first,followed by T.plicata and T.occidentalis.The final differentiation of T.koraiensis and T.standishii formed a clade.Enrichment analysis indicated that the PSGs of the North American Thuja species were involved in plant hormone signal transduction and carbon fixation of photosynthetic organisms pathways.The PSGs of East Asian Thuja were related to phenolic,alkaloid,and terpenoid synthesis,important stress-resistant genes and could increase plant resistance to external environmental stresses.This study discovered numerous aroma synthetic-related PSGs including terpene synthase(TPS)genes and lipid phosphate phosphatase 2(LPP2),associated with the synthetic aroma of T.sutchuenensis.Physiological indicators,such as the contents of soluble sugars,total chlorophyll,total phenolics,and total flavonoids were determined,which are consistent with the PSGs enrichment pathways associated with adaptive strategies in the five Thuja species.The results of this study provide an important basis for future studies on conservation genetics.

Comparative QTL Mapping of Resistance to Gray Leaf Spot in Maize Based on Bioinformatics

The integration QTL map for gray leaf spot resistance in maize was constructed by compiling a total of 57 QTLs available with genetic map IBM2 2005 neighbors as reference. Twenty-six ＂real QTLs＂ and seven consensus QTLs were identified by refining these 57 QTLs using overview and meta-analysis approaches. Seven consensus QTLs were found on chromosomes 1.06, 2.06, 3.04, 4.06, 4.08, 5.03, and 8.06, and the map coordinates were 552.53,425.72, 279.20, 368.97, 583.21, 308.68 and 446.14 cM, respectively. Using a synteny conservation approach based on comparative mapping between the maize genetic map and rice physical map, a total of 69 rice and maize resistance genes collected from websites Gramene and MaizeGDB were projected onto the maize genetic map IBM2 2005 neighbors, and 2 （Rgene32, htl）, 4 （RgeneS, rp3, scmv2, wsm2）, and 4 （ht2, Rgene6, Rgene8 and Rgene7） positional candidate genes were found in three consensus QTLs on chromosomes 2.06, 3.04, and 8.06, respectively. The results suggested that the combination of meta-analysis of gray leaf spot in maize and sequence homologous comparison between maize and rice could be an efficient strategy for identifying major QTLs and corresponding candidate genes for the gray leaf spot.

Positive Selection of CAG Repeats of the ATXN2 Gene in Chinese Ethnic Groups

The ataxin-2 （ATXN2） gene is located on human chromo-some 12q24.1. In normal individuals, the coding region in exon 1 of this gene has fewer than 31 CAG repeats （Yu et al., 2005： Laffita-Mesa et al., 2012）. However, an abnormal expansion of CAG trinucleotide repeats results in the aggre-gation of polyglutamine （polyQ）, which causes spinocer-ebellar ataxia type 2 （SCA2） （Pulst et al., 1996）. The expanded alleles have more than 32 repeats in the affected individuals, and generally there is an inverse correlation between CAG repeat length and age of onset （Pulst et al., 1996）. SCA2 is an autosomal dominant inheritance neurodegenerative disease, whose major clinical feature is progressive cerebellar ataxia. Atrophies of the brainstem and frontal lobe have been frequently detected by magnetic resonance imaging （MRI） （Yamamoto-Watanabe et al., 2010）. This disease has the strong effect on sensory and motor control.

Gene positioning and genome function

The eukaryotic genome is packaged as chromatin within the three-dimensional nuclear space. Decades of cytological studies have revealed that chromosomes and genes are non-randomly localized within the nucleus and such organizations have important roles on genome function. However, several fundamental questions remain to be resolved. For example, what is required for the preferential localization ofa gene to a nuclear landmark？ What is the mechanism underlying gene repositioning in the nucleus？ How does subnuclear gene positioning regulate gene transcription？ Recent studies have revealed that several factors such as DNA sequence composition, specific regulatory sequences, epigenetic modifications, chromatin remodelers, post-transcriptional regulators and nuclear architectural proteins can influence chromatin dynamics and gene positioning in a gene-specific manner among organisms from yeast to human. In this review, we discuss some recent findings as well as experimental tools to investigate subnuclear gene positioning and to explore its implications in genome functions.

GPS： a constraint-based gene position procurement in chromosome for solving large-scale multiobjective multiple knapsack problems

The multiple knapsack problem （MKP） forms a base for resolving many real-life problems. This has also been considered with multiple objectives in genetic algorithms （GAs） for proving its efficiency. GAs use self- adaptability to effectively solve complex problems with constraints, but in certain cases, self-adaptability fails by converging toward an infeasible region. This pitfall can be resolved by using different existing repairing techniques; however, this cannot assure convergence toward attaining the optimal solution. To overcome this issue, gene position-based suppression （GPS） has been modeled and embedded as a new phase in a classical GA. This phase works on the genes of a newly generated individual after the recombination phase to retain the solution vector within its feasible region and to im- prove the solution vector to attain the optimal solution. Genes holding the highest expressibility are reserved into a subset, as the best genes identified from the current individuals by re- placing the weaker genes from the subset. This subset is used by the next generated individual to improve the solution vec- tor and to retain the best genes of the individuals. Each gene＇s positional point and its genotype exposure for each region in an environment are used to fit the best unique genes. Further, suppression of expression in conflicting gene＇s relies on the requirement toward the level of exposure in the environment or in eliminating the duplicate genes from the environment.The MKP benchmark instances from the OR-library are taken for the experiment to test the new model. The outcome por- trays that GPS in a classical GA is superior in most of the cases compared to the other existing repairing techniques.

CRISPR-PIN:Modifying gene position in the nucleus via dCas9-mediated tethering

Spatial organization of DNA within the nucleus is important for controlling DNA replication and repair,genetic recombination,and gene expression.Here,we present CRISPR-PIN,a CRISPR/dCas9-based tool that allows control of gene Position in the Nucleus for the yeast Saccharomyces cerevisiae.This approach utilizes a cohesindockerin interaction between dCas9 and a perinuclear protein.In doing so,we demonstrate that a single gRNA can enable programmable interaction of nuclear DNA with the nuclear periphery.We demonstrate the utility of this approach for two applications:the controlled segregation of an acentric plasmid and the re-localization of five endogenous loci.In both cases,we obtain results on par with prior reports using traditional,more cumbersome genetic systems.Thus,CRISPR-PIN offers the opportunity for future studies of chromosome biology and gene localization.

Annual progress of clinical research on targeted therapy for nonsmall cell lung cancer in 2022

With the rapid development of lung cancer molecular detection and precisiontherapy, targeted therapy has covered the entire process of diagnosis andtreatment of nonsmall cell lung cancer patients. Overall mortality from lungcancer has decreased significantly over the past 20 years, especially since theintroduction of targeted drugs in 2013. In 2022, targeted therapy for lungcancer has developed rapidly. The optimization of treatment modes and theexploration of new target drugs such as antibody‐drug conjugates will broadenthe selection range of nonsmall cell lung cancer patients with positive drivergenes. This article reviews the latest advances in targeted therapy for drivergene‐positive lung cancer in 2022.